مادة االدوية

المرحلة الثالثة

محمد غدير حاتم. م. م

2016-2017

Diuretics

diuretic • Substance that increase the quantity of

urine or drugs inducing a state of increase

urine flow .

FUNCTIONS OF THE KIDNEY

• Water balance

• Electrolyte balance

• Plasma volume

• Acid-base balance

• Osmolarity balance

• Excretion

• Hormone secretion

Secretion of A-, BH+of bound and

unbound drug

Filtration @ Bowman’s capsule

Proximal tubule (PT)

(Site -1)

Descending thin limb (DTL)

(Site- 2_) Ascending

thin limb (ATL) (Site-3)

Thick ascending limb (TAL)

Distal tubule (DT)

(Site-4)

Collecting tubule (CT)

(Site-5)

The Nephron Contains Distinct Tubular Segments

Ureter

Renal vein

Renal artery

Cortex

Medulla

Collecting processes Papilla Minor calyx Major calyx

Gross Anatomical Features of the Kidney

filtration

SUBSTANCE FROM BOOOD INTO

NEPHRON OCCUR IN GLOMERULUS

TUBULAR REABSORPTION

Renal tubules reabsorb certain material from tubules to blood organ(Na 99% reabsorb) by two mechanism :

Cation exchange at site 1 and 4

Co2 + H2o ca H2co3 H+ Hco3

Chloride ion transport at site 2

Water reabsorption at site 5

TUBULAR SECRETION

•SECRETION OF hydrogen ion, K ion ,

weak acid and weak base

Site of action and diuretic along the

tubules of nephrone

• Site 1

• In proximal tubules

• Site 2

• Descending loop of henle

• Site 3

• Ascending loop of henle

• Site 4

• Distal covaluted tubules

• Site 5

• Collecting duct

Classification

1- osmotic diuretics

2-carbon anhydrase (low diuretic potency )

3- thiazide (moderate potency)

4--high efficacy diuretic (frusamide,

bumetanide )

5- potassium sparing diuretics

Osmotic diuretic

• Substance that are filtered through

glomerular such as Mannitol these

substance has ability to carriers waters

with them from cells with it into the urine

and decrease intracellular volume .

• These agent increase urine flow by

increase water excretion ,

• Na and Cl increase also excretion .

MECHNISM OF ACTION

•Trapped in tubular lumen and create

osmotic gradient

Clinical indication

1. Olige urea due to acute renal failure.

2. to decrease brain odema and

intracranial pressure .

3. Treatment of glucoma

4. In drug toxicity

Adverse effect

1. headache

2. Dryness of the mouth , thirst

3. Blurred vision, nausea , vomiting ,

thrombophelibitis and infection at site of

injection .

these agent given intravenous (50 – 200 )

gm over 24 hours because poorly oral

absorption .

Carbonic anhydrase inhibitors

less efficacious ) )

• Acetazolamid : its sulfonamide without

antibacteria activity . Action in the proximal

tubule.

• Mechanism of action

inhibit carbonic anhydrase enzyme on the

apical membrane of proximal and distal

tubules.

Carbonic Anhydrase Inhibitors (CAIs)

Site

of Action

• Carbonic anhydrase catalyze the reaction

of CO2 and H2O leading to H and HCO3.

blocking this enzyme block reabsorp of

HCO3 increase delivery of Na ,

K and HCO to distal nephron and finally

alkaline diuresis ( in PH )

Carbonic Anhydrase Function Act at the Proximal Tubule

HCO3-

70-85% reabsorbed

1. H+ exchanged Na+

2. HCO3-/Na+ co-tranport

3Na+

Therapeutic uses

1. Treatment of glucoma ( IOP ) by blocking enzyme in the cilliary body of the eye this lead to decrease of IOP .

2. Epelipsy : reduce severity and magnitude of the seizure

3. Mountain sickness (as a prophylaxis )

4. Adjunct in treatment of CHF or drug induced oedema

The drug is given orally once daily.

Adverse effect

1. Metabolic acidosis

2. Hypokalemia

3. Renal stone formation

4. Ca excretion

5. Drowsiness and parasthesia

Thiazides and related agent

(moderate diuretics)

• Mechanism of action

• Inhibition of Na / Cl contransporter inDCT

which lead to decrease Na reabsorpation

and increase Na /Cl excretion and

produce diuresis .

• Thiazid also increase K excretion and

promote Ca reabsorption .

Thiazide Diuretics

Site

of Action

Thiazides Mechanism of Action

Thiazides inhibit Na+/Cl- co-

transporter cause increase load

of Na+, excretion of K+ and H+,

Enhance PTH-regulated Ca+

reabsorption in the DT

Clinical uses

1-to treat mild to moderate hypertension due to reduction in extracellular fluid and plasma volume this lead to increase in urine flow and electrolyte excretion ,

2- to treat odema in congestive heart disease and nephrotic syndrome .

3- to treat idiopatheic hypercalciuria , because , thiazide it inhibit Ca excretion , this beneficial for patient with stone .

Adverse effect

1. Hypokalemia

2. Hypercalcemia

3. Hyperuricemia ( gout )

4. Muscle spasm or cramp

5. Hyper sensitivity reaction

6. Nausea ,constipation

7. Hypotention due to volume depletion

8. Allergic , skin rash .

Loop or high ceiling diuretic

(furosemide , bumetanide )

• Mechanism of action

inhibit the Na / K / Cl contransport of the

luminal membrane in the ascending limb

of the loop of henle therefore the

reabsorption of Na / K and Cl is decease .

Also increase the Ca content of urine .

Loop Diuretics Act on TAL

Site

of Action

Therapeutic uses

• 1-treatment of acute pulmonary edema of

congestive heart failure .

• 2- treatment of edema in patient become

resistance to thiazide.

Adverse effect

1. Hypotention due to rapid reduction in BP.

2. K depletion : hypokalemia

3. Cardiac arrhythmia

4. Hyperuricemia compete with uric acid for

renal secretary system thus blocking it

secretion and causing gouty attack .

5. Ototoxicity particularly when used with

the amino glycoside antibiotic .

K sparing diuretic

• These agent act on the DCT to inhibit K

secretion and H secretion .

• Eg : spironolactone . block aldosteron

receptor located in these tubules so

exchang of K with Na is inhibit ,resulting in

retention of K and excretion of Na .

K+-sparing Diuretics

Site

of Action

Clinical uses

1. Diuretic ( used in combination with thiazide

in hypertension to prevent hypokalemia

1. Secondary hyperaldosteronism

2. Congestion heart failure

the drug is given orally , rapidly absorbed ,

Onset of action 2-4 days , metabolized by liver.

MISCELLANEAUS DIURETICSS

• XANTHIN (caffein,theophyline)

• Naturally occurring produce mild diuresis

by increase blood flow to kidney so

increase GRF

• Cause CNS stimulation , hypotention

headach

Dental implication

1. Epinephrine in local anesthesia produce

transient hypokalemia this increase

cardiac arrhythmia .

2. Anti-inflammatory of

adrenocorticosteroid also promote

hypokalemia

3. Digitalis cause hypokalemia

4. NSAID antagonise the antihypertensive

effect of diuretic .

4- Increase syncope in patient taking

diuretic due to a depletion of

intravascular volume.

5- NSAID antagonize the antihypertensive

effect of diuretics .